This invention relates to the preparation of gossyplure.
Gossyplure, a mixture of 7,11-hexadecadienyl acetate stereoisomers, is a known pheromone for several insect species. In order to make this compound widely available for use in insect control, economic large scale synthetic conversion processes must be developed. While synthetic routes for the preparation of gossyplure have been disclosed in the prior art, the known routes suffer from the disadvantages of requiring multiple reaction steps with consequent low over all product yield, consumption of large quantities of reagents which do not contribute to the final product structure and the like.
For example, in U.S. Pat. No. 3,919,329 (1975), Anderson and Henrick disclose a multistep synthesis which involves (1) the oxidation of 1,5-cyclooctadiene to 1,2-epoxy-5-cyclooctene, (2) oxidation of the epoxide to 2-hydroxy-5-cycloocten-1-one, (3) oxidative cleavage of the .alpha.-hydroxyketone to an alkyl-8-oxo-4-octenoate, (4) Wittig reaction of the octenoate to yield (4Z,8Z/E)-4,8-tridecadienoate, (5) reduction of the dienoate to a dienol, (6) conversion of the dienol to the mesylate, which is then (7) converted to the iodide or bromide, which is finally (8) coupled with a cuprate reagent prepared from cuprous iodide and the lithium reagent obtained from the reaction of lithium and the bromo-acetal obtained from 3-bromo-1-propanol and ethyl vinyl ether. The product acetal is (9) hydrolyzed to 7,11-hexadecadienol, and finally (10) converted into the acetate using acetic anhydride in pyridine.
In U.S. Pat. No. 3,996,270 (1976), Friedman and Canan describe an alternative multistep synthesis of gossyplure which involves (1) butylation of the mono-anion of 1,5-hexadiyne, (2) partial reduction of the resulting 1,5-decadiyne in sodium/liquid ammonia to yield deca-(E)-5-enyne, (3) alkylation of the enyne with hexamethylene halohydrin or a protected derivative thereof, (4) acetylation of the product of step (3), which product is then (5) partially reduced in the presence of hydrogen and Lindlar catalyst. This synthesis requires several starting chemicals which are not readily available on large scale, e.g. 1,5-hexadiyne and hexamethylene halohydrin, and depend for the desired product stereochemistry on two separate hydrogenation steps.
Yet another multistep synthetic route for the preparation of gossyplure has been proposed by Muchowski and Venuti, as disclosed in U.S. Pat. No. 4,296,042 (1981). Thus, (1) an omega-hydroxyalkyl diphenyl phosphine is converted into a cyclic polymethylene 1,1-diphenyl phosphonium bromide, (2) the cyclic phosphonium bromide is then converted into a cyclic phosphonium ylid by treatment with an alkali metal alkoxide, then (3) coupled with a protected aldehyde or ketone to produce a phosphine oxide. The phosphine oxide is (4) treated with an organolithium compound, then (5) coupled with a second aldehyde and finally (6) the resulting lithium salt is decomposed, producing a crude, protected dien-ol. The protected dien-ol is (7) hydrolyzed and esterified by treatment with acetic acid/acetyl chloride. Again, numerous reaction steps are required as the desired chain length and stereochemistry are achieved in a piecemeal fashion.
In summary, due to the large number of reaction steps required, the relative inavailability of many needed reagents and the step-wise fashion in which the desired carbon backbone is constructed, known synthetic routes for the production of gossyplure are not amenable to being carried out economically on a large scale.